Hepatitis B vaccine (HBVacc) protects against hepatitis B, a major infectious disease that can cause cirrhosis and hepatocellular cancer. The vaccines developed to date are generally effective and safe. However, HBvacc has been implicated in the pathogenesis of autoimmune phenomena. Crossreactivity with HBsAg epitopes, yeast antigens, and toxic or other immune-mediated phenomena caused by adjuvants has been considered responsible for the induction of HBvacc-mediated phenomena. Particular attention has been given to the alleged association between HBvacc and multiple sclerosis (MS) and other immune-mediated neurological associations. This chapter discusses in great detail the role played by HBVacc in the development of autoimmune diseases, including MS and other neuromuscular disorders, autoimmune skin and vascular disease, and other autoimmune diseases.